Comparison of the lung delivery of a cisplatin dry powder using endotracheal administration and nose-only inhalation in rats
Pauline Percier1, Tamara Davenne1,2,3, Ismaël Hennia1, Baptiste Mingers1, Karim Amighi2 and Rémi Rosière1,2
1InhaTarget Therapeutics, Rue Antoine de Saint Exupéry 2, 6041 Gosselies, Belgium
2Unit of Pharmaceutics and Biopharmaceutics, Université libre de Bruxelles (ULB), Brussels, Belgium
3 Laboratory of Immunobiology, U-CRI, Rue Adrienne Boland 10, 6041, Gosselies Belgium
Preclinical studies remain necessary for the development of inhaled therapies. The devices used for lung delivery of inhaled formulations to rodents can be classified as passive exposure devices (e.g., nose-only exposure) or endotracheal devices. Endotracheal devices are used at early-stage of development when a limited amount of drug formulation is available whereas nose-only inhalation devices are used in more advanced non-clinical stages such as in pivotal GLP studies. The preclinical development of a cisplatin dry powder for inhalation (CIS-DPI) followed this approach with the use of both devices at different stages of preclinical development. In the present study, we compared the administration of CIS-DPI using an endotracheal device and a nose-only exposure system in rats. The two routes of administration resulted in different exposures to cisplatin, with higher exposure in the lungs and plasma following endotracheal administration at the same cisplatin dose. The upper airways (the nasal cavity in particular) were very sensitive to cisplatin and endotracheal route bypassed the upper airways, which led to higher overall tolerance to CIS-DPI following endotracheal administration.
The endotracheal and nose-only inhalation devices resulted in different exposure to a cisplatin dry powder in the respiratory tract in rats. Endotracheal administration, by bypassing the upper airways, induced a greater deposition in the lungs and better tolerance in the respiratory tract at the same dose of CIS-DPI than the nose-only inhalation device.